The broad objective of this research proposal is to obtain insights into the processes which control the synthesis, degradation (renewal), and assembly of changes in transcription of individual messenger RNAs in the abrupt stimulation, or inhibition of protein synthesis which occurs during the experimental development or regression of cardiac hypertrophy. We will evaluate the role of changes in the relative concentrations of tRNA isoaccepting species, and in the level of their charging with amino acids in the control of synthesis and degradation of myofibrillar proteins. We will also study compartmentalization of the amino acid precursor pool in heart muscle with the aim of characterizing the process of reutilization, of amino acids derived from protein degradation, for protein synthesis. We will directly compare the specific activities of aminoacyl tRNA, total free intracellular amino acid and extracellular amino acid pools during periods of rapid protein synthesis and degradation, to determine if there is a preferential shunting of amino acids derived from protein degradation into the aminoacyl tRNA pool. The possibility of non-random assembly and turnover of myofibrillar proteins will be evaluated. We also plan to study changes in RNA transcription, protein translation and the proliferative response of cardiac mitochondria, to stimuli that lead to the rapid accumulation or removal of mitochondria.